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Blood Transfusion Reactions
(BTR) & the Blood
Bank:Explaining the Link
Objectives
• Early identification of common transfusion
reactions
• Differentiate life threatening reactions from
benign transfusion reactions
• Manage common immunologic transfusion
reactions.
Immune mediated transfusion reactions
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Febrile non hemolytic tranx rxns
Immune mediated hemolysis
---Acute and delayed hemolytic reactions
Anaphylactic transfusion rxns
Urticarial transfusion rxns
Post-transfusion purpura
GVHD
TRALI –Transfusion Related Acute Lung
Injury (pulm leuko-agglutinin reactions)
Non immune mediated reactions
• Physical reactions: thermal i.e. heat or cold
induced
• Infectious; Hepatitis B/C, malaria, HIV, etc.
• Chemical; citrate toxicity,
hypo/hyperkalemia, iron overload
• Acute hypotensive reaction: mediated by
bradykinins and occurs in patients with
faulty bradykinin metabolism on ACE I
• Osmotic injury
• Congenital and acquired hemolytic anemias
What to DO ?
• Early recognition of signs/symptoms suggestive
of a transfusion reaction and prompt reporting to
the blood bank are essential.
• The most common symptoms are chills, rigors,
fever, dyspnea, light-headedness, urticaria,
itching, and flank pain. If any of these symptoms
(other than localized urticaria and itching) (?)
occur, the transfusion should be stopped
immediately and the IV line kept open with
normal saline.
• What to DO?
• The remainder of the blood
product and clotted and
anticoagulated samples of the
patient's blood should be sent to
the blood bank for investigation.
Immunologic Reactions
classic blood transfusion reaction are usually immunologic and
occur to interactions of inherited/ acquired Ab with foreign Ag
from transfused blood
Incidence of rxns
-most common cause is transfused of non-matched
blood mostly to clerical error
-2x more common in infants than adults
-more common in patients with hematological and
oncological conditions
Febrile Non Hemolytic Tranfusion
Reactions(FNHTR)
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•
•
Most common, usually benign without sequela
A least rise of temp. of 1o C
15% will have a reaction in the future with
subsequent transfusion
Etiology
1. Class 1 HLA Ab (HLA 5)directed against
contaminating WBC in red cell concentration
2. Cytokines IL-1, 6,8 and TNF alpha generated in
stored blood/products
Management
Discontinue transfusion, rule out hemolysis i.e.
check labels, repeat type and cross, coombs test
Prevention
• Leukoreduction
Acute Hemolytic Reactions
• Rapid destruction of RBC immediately after
within 24 hours of transfusion.
• Occurs due to rapid transfused RBC
destruction by preformed recipients Abs
• IgM mediated complement fixation leading
to rapid intra vascular hemolysis
• Most common causes are clerical or
procedural errors
Acute hemolytic rxns
• Clinical presentation
• Classic presenting triad of Fever, flank
pain and reddish brown urine from
hemoglobinuria.
• DIC may be presenting mode
Conditions – destroy donor cells
• Naturally occuring or stimulated
alloantibodies (anti-A, Kell, Jka , Fya)
• Autoantibodies
• Drug-associated antibodies
• Bacterial Contamination
Conditions –destroy recipient cells
• Incompatible (ABO)
• Infusion of large amount of hypotonic
solutions
• Mechanical Trauma
Actions ?
• If AHTR is suspected, one of the first steps is to
recheck the sample and patient identifications.
Diagnosis is confirmed by measuring urinary Hb,
bilirubin, and haptoglobin.
• Intravascular hemolysis produces free Hb in the
plasma and urine; haptoglobin levels are very
low. Hyperbilirubinemia may follow.
• After the acute phase, the degree of acute renal
failure determines the prognosis.
• Prolonged oliguria and shock are poor
prognostic signs.
Laboratory Tests
Patient Samples
-Reconfirmation of ABO, Rh type and
Antibody screen and Direct Coombs Test, and Antibody
identification
- CBC
-Urinalysis (to document hemoglubinuria)
- Serum bilirubin
- BUN, Creatinine and Quantitation of Urine
Output
-Coagulation screen- PT, PTT,TT,FDP,
Fibrinogen levels
Product Samples- Reconfirmation and ABO and Rh typing
and antibody screen results
Laboratory evaluation of suspected
hemolytic reaction
• The work up of suspected transfusion reaction includes :
1.Check all the records to ensure that the correct unit of
blood was transfused to the right patient. This includes :
- Patient’s details
- Blood requisition form
- Compatibility report
- Labels
Laboratory evaluation of suspected hemolytic
reaction
Clerical errors
a. Incorrect labeling
- recipient’s sample
- blood bag
- pilot tubes
- request form
b. Misidentification of patient at time of collection
of sample or transfusion of blood
c. Mix-up of samples at time of collection.
Laboratory evaluation of suspected
hemolytic reaction
• Till the time a clerical error is not ruled out,
stop issuing of all blood units from the
blood bank, as it may lead to issue of
another mismatched blood due to mix-up
of samples or other clerical errors.
Laboratory evaluation of suspected
hemolytic reaction
• 2. Technical errors
a. Error in blood grouping of donor and recipient
samples
b. Error in compatibility testing
- faulty technique
- weak antibodies not detected by routine tests
3. Destruction of recipient red cells by donor
antibodies. This occurs due to indiscriminate use
of group 0 blood which may contain potent antiA and anti-B.
Laboratory evaluation of suspected
hemolytic reaction
• The following samples must be immediately
sent to the laboratory and blood bank.
- Post transfusion sample in plain vial (5m1)
- Post transfusion sample in EDTA vial (3m1)
- Blood bag along with transfusion set
- Urine (post-transfusion) 1st sample
- Coagulation profile-citrated blood sample
- Blood cultures from the blood bag and the
patient
Laboratory evaluation of suspected
hemolytic reaction
• The pre-transfusion sample should be preserved in the
laboratory for 7 days.
For evaluation of a patient with hemolytic
reactions the investigation may be divided into
three:
1. Investigation for evidence of increased red
cell destruction
2. Investigation for identification of cause of
hemolysis
3. Investigation to follow up of a patient with
proven hemolysis
Tests for evidence of increased red cell
destruction
•
1. Centrifuge the post-transfusion blood sample and
examine the supernatent plasma.
• Compare this with the pre-transfusion sample. A pink or
red colour in the post-transfusion sample indicates
hemolysis and presence of free hemoglobin.
2. Perform a Direct antiglobulin test (DAT) on the posttransfusion sample. A positive test indicate immune
hemolysis. A negative DAT with hemoglobinemia
suggests a non-immune hemolysis e.g. due to
mechanical trauma or thermal damage.
Tests for evidence of increased red cell
destruction
•
3. Reticulocyte count is raised in patient
with hemolysis.
4. Pre-and post hemoglobin value.
5. Serum unconjugated bilirubin
estimation.
Tests to establish the cause of hemolysis
1. Repeat ABO and Rh grouping on the pre-and
post-transfusion samples and from the bag. If
blood group of the pre-and post-transfusion
sample do not agree, it may be due to error in
patient identification, drawing or grouping of
blood. Another patient’s sample may have been
drawn at the same time and labeled incorrectly.
If the donor sample is not of the same group as
indicated on the bag, an error in labeling or
grouping and also in the compatibility testing
should be suspected
Tests to establish the cause of hemolysis
• 2. Repeat the compatibility testing on pre-and posttransfusion samples with a sample of blood from the
bag. The testing must be done using saline,
enzyme/albumin and indirect antiglobulin techniques. If
both the samples show incompatibility- an error in the
pre-transfusion testing.
• The donor sample may have been incorrectly labelled or
the crossmatch reaction was incorrectly read as
negative.
If the incompatibility is seen only with the postransfusion
sample, an anamnestic response should be suspected.
• If both crossmatches are compatible and there is a
strong suspicion of hemolysis, further tests are required.
Tests to establish the cause of hemolysis
• 3. Perform an antibody screening on the preand post-transfusion samples. If an antibody is
detected, it should be identified.
• An antibody in the post transfusion sample may
be due to
- Anamnestic response (e.g. anti-Kidd, anti-MNS
and anti-Duffy antibodies)
- Passively acquired antibody from donor
plasma.
Antibody screening must be done..
Tests to establish the cause of hemolysis
• 4. Examine a stained
peripheral blood film
for spherocytes and
crenated cells,
presence of which
favors a diagnosis of
immune hemolysis.
Tests done to follow up a patient with
proven hemolysis
• 1. Test sample for serum unconjugated
bilirubin levels
• 2. Measure plasma hemoglobin levels.
• 3. Serum haptoglobins are reduced.
Tests done to follow up a patient with
proven hemolysis
• 4. Examine the post-transfusion urine
sample for free hemoglobin.
• Done in a freshly collected sample of
urine. In the event of delay in evaluation of
a hemolytic reaction, the urine may be
tested for hemosiderin.
• The presence of intact red cells indicates
hemorrhage and not hemolysis.
Tests done to follow up a patient with
proven hemolysis
• 5. Perform a coagulation screen
(PT,PTT,TT) and platelet count to
check for DIC.
6. Monitor blood urea & serum
creatinine to assess renal function.
Tests for non-immune hemolysis
•
1. Examine the bag for discoloration or clots, any abnormal mass,
foul small or a fuzzy cell: plasma interface. Take specimens from the
bag for culture at 4°C, 20°C and 37°C for bacterial and fungal
cultures and also for gram’s staining.
• 2. Examine the plasma in the bag for presence of free hemoglobin. If
present, it indicates improper storage of the unit of blood over
heating or over-cooling ,injection of drugs or hypotonic solutions.
Presence of free hemoglobin in the administration tubing suggests
that the same tube was used for administration of dextrose/other
solutions.
• 3. The possibility of mechanical/osmotic hemolysis should also be
suspected
Delayed hemolytic transfusion rxns
Generally occurs within 3-10 days of tranx
Usually due to senescent Ab response on re-exposure
to a foreign red cell Ag . The Ab was not detected in
pretransfusion testing.
History of previous pregnancy, transfusion or transplant
Usually extra vascular and is less severe than acute
Other Abs often Rh and Kidd
Clinical presentation
Falling HCT, low grade fever, slight increase in indirect
bilirubin, spherocytes on blood smear
Delayed hemolytic transfusion
rxns
• Laboratory features
1. A fall in hemoglobin not attributed to any other cause.
• 2. Appearance of a new alloantibody.
• 3. Spherocytosis is observed in blood films which may
be the only indicator.
• 4. Direct antiglobulin test is positive. The test becomes
positive a few days after transfusion and remains until all
incompatible cells have been eliminated.
Delayed hemolytic transfusion
rxns
• 5. Antibody detection .
The antibody is detected 4-7 days after
transfusion and peaks after 10-15 days
Sensitive antibody detection techniques in
pretransfusion testing may prevent DHTRs.
Delayed hemolytic transfusion
rxns
• Antibodies associated with DHTR :
anti-c, anti-E
anti-A, anti-B (IgG)
anti-Kell
anti-Fya,-Fyb
anti-Jka,-Jkb
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